High energy neutron radiotherapy is a new and potentially useful means of treating cancer. Clinical trials are underway to evaluate this treatment modality alone or mixed with conventional gamma irradiation and soon, a greater number of combination neutron-chemotherapy treatments will be clinically in use. There is clearly a need for experimentation with these modalities. The proposed experiments are designed to study the effects of 25 MeV neutrons (average energy) alone or in combination with the S phase specific cytotoxic agents hydroxyurea or cytosine arabinoside on the intestinal cell renewal system of mice. The "recruiting" effect of low doses of clinically useful high energy neutrons on surviving cells observed with lower energy irradiation will be evaluated by employing techniques to discern slowly or non-cycling cells from rapidly cycling cells. Investigations into the mechanism of the post neutron treatment response of surviving cells will be done by comparing the degree of cytotoxicity with the degree of "recruitment." Post treatment change of proliferative characteristics of normal or tumor tissue should influence the outcome of a combined chemotherapy and radiation treatment or a single modality fractionation treatment. Further studies will be done to see if the mechanisms for the proliferative change is direct or indirect by irradiating the upper thorax and head region of mice with 25 MeV neutrons and evaluating possible "recruitment" of stem cells in the shielded intestinal system. The influence of a change in stem cell proliferative characteristics on possible sublethal damage after high energy neutron treatment will be evaluated by experiments to compare split dose recovery before and after "recruitment." Intestinal stem cell survival after various intervals of time between the two drugs and neutron exposure will be measured using the microcolony assay to evaluate the result of these drugs on stem cell survival. The results of these experiments will provide information to better evaluate the promise and potential of neutron radiotherapy.